RET and Hirschsprung disease: Since mutations in RET and EDNRB are the most frequent genetic changes encountered in familial cases of HSCR (EDNRB mutations detected in ~5% of HSCR patients) [8], our data, together with those of Young et al. [38], suggest that reduced ENCC migration is a key pathogenic mechanism underlying failure of ganglia formation in the distal colon of HSCR patients.